AB0479 BARICITINIB AND UPADACITINIB AFFECT THE LEVELS OF BONE DESTRUCTION MARKERS AND BONE FORMATION INDICATORS IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: A. Felis-Giemza, W. Kurowska, M. Marecka-Kuzdub, E. Kuca-Warnawin, M. Massalska, W. Maśliński
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Janus kinase inhibitors (JAKis) baricitinib and upadacitinib inhibit the radiographic progression of joint damage in patients with rheumatoid arthritis (RA) [1-3]. Recent findings indicate that treatment with JAKi can lead to the repair of arthritic bone erosions [4]. However, although the immunomodulatory effects of JAKis have been extensively studied in inflammatory diseases, the effects of JAKis on bone metabolism in patients with RA are not fully understood. <h3>Objectives</h3> To investigate the effect of baricitinib and upadacitinib on the levels of bone destruction markers and bone formation indicators in the peripheral blood of patients with RA. <h3>Methods</h3> The study included 14 patients with RA (all women, aged 23–65 years, mean age 47.7 ± 12.4 years) with high disease activity at baseline (median DAS 28-ESR 5.625, range: 5.11–7.17); median ESR 11.50 mm/h (range 5.00–60.00 mm/h); median CRP 12.15 mg/ml (range 1.00–40.00 mg/ml). Peripheral blood plasma samples were collected from patients prior to JAKi treatment, and during therapy with baricitinib 4 mg once daily (n=9) or upadacitinib 15 mg once daily (n=5). Concentrations of C-telopeptide fragments of type I collagen (CTX-I), osteocalcin, Receptor Activator for Nuclear Factor κ B Ligand (RANKL), and osteoprotegerin (OPG) were measured in plasma by the enzyme-linked immunosorbent assays. Changes in the variables were assessed using paired Student t-test or Wilcoxon matched-pair signed rank test (depending on the type of data distribution). P-values &lt;0,05 were considered significant. <h3>Results</h3> The median duration of treatment with JAKi was 12 months (range 7–18 months). Eleven (78.6%) patients were treated for more than 12 months. The effects of JAKis were analyzed in two-time intervals: after 5-8 months of therapy and after 12 months of therapy. The median DAS 28-ESR decreased to 2.83 (range 1.13–7.56, p=0,014), after 5-8 months of therapy, and to 2.53 (range 0.75–7.34, p=0.002) after 12 months of therapy. The concentration of bone turnover marker CTX-I decreased gradually during JAKi treatment from a median pre-treatment level of 247.1 ng/ml (range 50.0–1228.0 ng/ml) to 186.0 ng/ml (range 0.0–394.0 ng/ml) after 5-8 months of therapy, and 78.0 ng/ml (range 0.0–481.0; p=0.031) after 12 months of therapy. Conversely, treatment with JAKi resulted in a gradual increase in the median osteocalcin concentration from a pre-treatment level of 17.0 ng/ml (5.0–37.0 ng/ml) to 24.0 ng/ml (6–92 ng/ml) and 28.6 ng/ml (11.0–43.0 ng/ml) after 5-8 months and 12 months of therapy (p=0.027), respectively. In a subgroup of 6 patients (2 treated with upadacitinib and 4 treated with baricitinib), a decrease in RANKL/OPG concentration ratios were observed after 5-8 months or/and after 12 months of therapy (from pre-treatment median ratio of 0.23, range: 0.09–1.26 to 0.11, range: 0.00–0.87 after therapy; p=0.03). In 5 patients, the RANKL/OPG ratio did not change during treatment with baricitinib or upadacitinib. <h3>Conclusion</h3> The decrease in the concentration of CTX-I, a marker of bone destruction, with a simultaneous increase in the concentration of osteocalcin, a marker of bone formation, and a decrease (at least in a subgroup of patients) in the concentration of RANKL, a stimulator of bone resorption, in relation to its receptor-decoy OPG, suggests that treatment with baricitinib and upadacitinib may promote bone anabolic processes in patients with RA. <h3>References</h3> [1]van der Heijde D, et al. RMD Open, 2018. doi: 10.1136/rmdopen-2018-000662. [2]Taylor PC, et al. N Engl J Med, 2017. doi: 10.1056/NEJMoa1608345. [3]Fleischmann R, et al. Arthritis Rheumatol, 2019. doi: 10.1002/art.41032. [4]Adam S, et al. Transl Med, 2020. doi: 10.1126/scitranslmed.aay4447. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.